Transcriptomic and Metabolomic Mechanism of Ibuprofen, Chondroitin Sulfate, and Vitamins With Minerals Tablets (21) for Kashin–Beck Disease Treatment

ABSTRACT Background Kashin–Beck disease (KBD) is an osteoarthropathy with no specific drug treatment. This study seeks to uncover the molecular mechanisms of ibuprofen, chondroitin sulfate, and vitamins with minerals tablets (21) in treating KBD. Methods Integrated transcriptomic and metabolomic analyses were performed on peripheral blood samples collected from four KBD patients before and 1 month after treatment. Differential gene expression was assessed using the DESeq package, while differential metabolites were identified through univariate and multivariate statistical analyses. Results After treatment, 5671 differential genes (|log 2 FC| ≥ 1, q < 0.05) were identified, with 4954 upregulated and 717 downregulated. Enriched pathways included PI3K‐Akt, MAPK, ECM‐receptor interaction, Rap1, and Ras signaling. Untargeted metabolomics analyses revealed five differentially expressed metabolites (VIP ≥ 1, |log 2 FC| > 0.58, p < 0.05): L‐glutamine, 2‐methylpropan‐2‐amine, epsilon‐caprolactam, phosphocholine, and 1‐palmitoyl‐2‐linoleoyl‐sn‐glycero‐3‐phosphocholine. Metabolite enrichment analysis suggested alterations in amino acid and fatty acid metabolism. Integrated analysis revealed key pathways such as alanine, aspartate, and glutamate metabolism and arginine biosynthesis. Conclusions The combination of ibuprofen, chondroitin sulfate, and vitamins with minerals tablets (21) may alleviate KBD through modulation of key genes (GDNF, BDNF, CCL2, VEGFA, and PPARG) and glutamine‐related metabolic pathways.